FDA begins process to remove breast cancer indication from Avastin label

FDA is recommending removing the breast cancer indication from the label for Avastin (bevacizumab) because the drug has not been shown to be safe and effective for that use.

The agency is making this recommendation after reviewing the results of 4 clinical studies of bevacizumab in women with breast cancer and determining that the data indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. These risks include severe high blood pressure; bleeding and hemorrhage; the development of perforations in the body, including in the nose, stomach, and intestines; and heart attack or heart failure, according to an FDA news release.

In July 2010, after reviewing all available data an independent advisory committee, composed primarily of oncologists, voted 12-1 to remove the breast cancer indication from Avastin’s label.

“This will be the first of many reviews of follow-on studies of approved products or comparative effectiveness evaluations that are being done by various third parties, all of which can derail or limit approved indications by FDA,” Randy Vogenberg, PhD, RPh, principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access Finance program at The Jefferson School of Population Health in Philadelphia, told Formulary.

“In addition, health plans or PBMs will most likely become more aggressive in using not only FDA actions to effect approved product use or formulary positioning, but their own data to make usage recommendations or formulary positioning to drive more evidence-based coverage,” Dr. Vogenberg said. “This would build upon National Comprehensive Cancer Network guidelines-or similar compendia-and be more timely in being put into effect in the marketplace.”

According to FDA, removing the breast cancer indication from the Avastin label will be a process. This is the first step. The drug itself is not being removed from the market and today’s action will not have any immediate impact on its use in treating breast cancer. Today’s action will not affect the approvals for colon, kidney, brain, and lung cancers.

Oncologists currently treating patients with bevacizumab for metastatic breast cancer should use their medical judgment when deciding whether a patient should continue treatment with the drug or consider other therapeutic options.

The agency has informed Genentech, Avastin’s manufacturer, of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech has not agreed to remove the breast cancer indication voluntarily, so the agency has issued a Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agency’s determination. The company has 15 days to request a hearing; if it does not do so, the hearing will be waived and FDA will begin proceedings to remove the breast cancer indication.

"We believe women living in the United States with metastatic HER2-negative breast cancer should also have Avastin as a treatment option, and, therefore, we will request a hearing with the FDA,” said Genentech’s Hal Barron, MD, chief medical officer and head, Global Product Development, in a company press release.